The invention relates to an implant element for permanent anchorage in bone tissue in which at least the surface intended to face the tissue in the implantation region is made of a biocompatible material such as titanium and having a clinically well documented surface.
It is previously well established to use medical implant elements for a variety of purposes. Specifically, in the dental field Brxc3xa5nemark System(copyright) implants for replacement of lost dental roots have been successfully used for 30 years. The treatment comprises three stages: (1) One or more titanium screws are installed in the jawbone and are left to integrate with the bone for between three and six months, (2) Special abutments are connected to the fixtures, (3) When the gums have healed, the dental prosthesis is fitted, for permanent use and providing a similar feeling as with natural teeth.
Titanium is a lightweight metal with high strength, low thermal conductivity and fine corrosion resistance. The most important property in this context is the unique bio-compatibility of titanium which might be related to the spontaneous formation of titanium oxide on its surface. Brxc3xa5nemark System(copyright) is based on the ability of titanium to integrate permanently with bone tissue, which is a medical phenomenon named osseointegration.
The implant screws are machined from commercially pure titanium. The surface topography of the machined surface shows features in the micron range. According to U.S. Pat. No. 4,330,891 the interaction processes between the titanium oxide surface and the surrounding tissue which results in implant-bone integration are improved if the implant surface is micro-pitted with pits having a diameter in the range of from 10 nm up to about 1000 nm, i.e. the size of the micro-pitting approaches the order of magnitude of the cell diameter in the surrounding tissue or a few multiples thereof.
In addition to a well-defined implant surface topography special care also has to be taken with respect to the surgical technique to assure that the prerequisites for achieving osseointegration are fulfilled. The implant screws are normally installed in the bone tissue at a first operation. Thereafter they are left unloaded for a period of three to six months covered by the soft tissue. At a second surgical session the soft tissue covering the implant screws is removed and the screws are connected to a superstructure and loading can be permitted.
It is assumed that such a two-stage surgical procedure with an early post-operative period without loading is important for the implant stability during the early healing phase. However, the two-stage surgical technique is a disadvantage for the patient and makes the installation time-consuming and therefore expensive. It has also been demonstrated that for specific indications a correct clinical bone anchorage can be achieved using a non-submerged approach, i.e. a one-stage surgical procedure. Also in case of such a one-stage surgical procedure it is assumed that a critical healing period, approximately three months long, during which unfavourable loading should be avoided, is important in order not to jeopardize the process of osseointegration.
Specifically in the mandibular bone the success rate for this type of dental implants is very high. However, in the maxilla and the posterior mandible the success rate very much depend on the quality of the bone.
An object of the present invention is to provide an implant element which allows for a possible reduction of the healing period but which still guarantees a long term stability during clinical loading conditions.
A further object of this invention is to increase the possibilities to use the implants more successfully also in low bone qualities, which is often the case in the maxilla and the posterior mandible.
A review of the literature shows that implant mobility and radiographic bone loss are associated with failures; either to early (primary) failures or late (secondary) failures. The early failures are the consequence of biological processes which interfere with the healing process of bone and the establishment of osseointegration. The majority of these failures are host-related, whereas late failures are the consequence of mainly overload and host-related factors. Clinical retrieval studies indicate that a high degree of bone-implant contact is a consistent finding in functioning, successful clinical osseointegrated titanium implant systems (Sennerby et al, 1991). On the other hand, ongoing studies show that clinically mobile implants with radiolucency are characterized by absence of bone and the presence of fibrous capsule formation and inflammatory cells.
On the basis of available literature and knowledge it may therefore be concluded that the integration of titanium implants and bone and the maintenance of this integration are prerequisites for the clinically documented long-term function and relatively high success rate with this implant. However, experimental studies have shown that bone is not formed directly on the surface of the titanium implant. Instead the process of bone formation originates from existing bone surfaces and solitary islands of bone either in the bone marrow distant from the implant surface or in the distal threads. The bone formation is directed towards the titanium surface and the immediate interface zone is the last to be mineralized (Sennerby, Thomsen, Ericson, 1993a; 1993b). The early phase of bone healing is therefore of particular importance for the establishment of osseointegration. If the healing process is jeopardized, for instance by insufficient implant stability in bone of poor quality or other negative factors, such as previous irradiation of tissues or local inflammation, osteopenia and rheumatoid arthritis the implant-bone connection may be inadequate and the implant-bone structure may not withstand loading (Sennerby and Thomsen, 1993; xc3x96hrnell et al, 1997, Brxc3xa5nemark et al, 1997). It is therefore an urgent need to improve the treatment of patients with the osseointegrated implant technique in case of non-optimal conditions. Such improvements may allow patients with a non-optimal, deranged and/or damaged tissue structure to benefit from treatment with osseointegrated implants.
It is previously known that coatings of biocompatible material of controlled chemical composition and crystalline structure may be deposited onto a substrate to provide articles to be used as medical, dental or orthopedic implants. An objective of such deposition or coating is to develop an implant with a surface which provides for a stable bone-implant connection.
An example of a suitable biocompatible material in this context is hydroxylapatite, i.e. Ca10(PO4)6(OH)2, and mixtures of calcium-phosphates, CaP, which resemble the primary inorganic chemical constituent of bone. Various attempts have been made to deposit CaP coatings onto metal substrates in which case the CaP mixture is acting as a biocompatible coating.
According to several scientific investigators, see for example Dhert 1992, CaP coatings may stimulate bone growth during an initial stage. However, the long term results are not convincing, see for instance Johnson B W et al (1992), Lemons J E et al (1988) and Gottlander and Albrektsson 1991.
A possible explanation for the poor long term results may be that the coatings which have been used so far normally have been plasma-sprayed to a thickness of 50-100xcexcm. Such coatings may have an inherent significant probability for fractures, which may be due to in vivo dissolution and the insufficient mechanical strength of the relatively thick coatings.
A review of the literature reveals that, in addition to the plasma spraying, there are several methods to prepare surface coatings. One way to classify these methods is to divide them into (1) those methods where a coating is prepared by xe2x80x9cdry depositionxe2x80x9d and (2) those methods where xe2x80x9cwetxe2x80x9d coating techniques are used.
The former methods include (i) plasma spraying, (ii) laser ablation, (iii) ion assisted sputtering and (iv) radio frequency (RF)-sputtering. The xe2x80x9cwetxe2x80x9d preparation techniques include: (i) dipping samples into a solution, (ii) electrolytically assisted CaP deposition and (iii) precipitation from supersaturated solutions.
None of these techniques is new per se; the principles underlying each method and the processing technologies used by each of them are in general well established and have been described in numerous publications, in particular with regard to formation of thin high Tc-superconducting films, optical coatings, hard film coatings etc. These methods will therefore not be described in any detail here.
In the following the different coating techniques will be discussed with respect to their advantages and drawbacks with respect to an implant element.
Plasma Spraying
Up to now plasma spraying (PS) has been by far the most commonly used method for producing CaP coatings. However, by this method only comparatively thick coatings have been produced, i.e. coatings having a thickness down to about 10 xcexcm, but not thinner.
An object of our invention is to provide a substantially thinner CaP coating, since the probability for fractures will decrease with decreasing coat thickness. Therefore, the plasma spraying technique is not suitable.
Furthermore considerable amounts of impurities may be dispersed within the coating when the plasma spraying method is used in ambient air, for example an appreciable amount of carbonyls may be embedded in the CaP coating. Our invention describes an implant element which is prepared according to a well-controlled process without introduction of impurities.
Scanning Electron Micrograph (SEM) pictures of the surface morphology produced by a typical PS deposition technique shows a rough surface on at least 50 xcexcm scale with a large variety of appearing structures. The surface structure which is obtained by the PS technique is dramatically different from the structure of the underlying substrate surface, for instance a titanium surface in case of a titaniun dental implant element.
Furthermore, it is usually necessary to have a rough underlying surface in order to obtain sufficient adhesion of the coating when using the PS technique. However, we can not allow for such surface roughening in the present invention since we wish to preserve the clinically well documented underlying surface.
Laser Ablation
Laser ablation is a relatively new deposition method that is able to produce a superior quality, comparatively thin high Tc superconducting film coating. This method has also been used for depositing calcium-phosphate coatings.
It has been illustrated that the surface of a laser ablated film is rough on the micrometer scale with a broad diameter distribution of spherical particles. Thus, the coating does not follow the underlying substrate surface morphology.
Ion Beam Assisted Sputtering and Ion Beam Sputtering
These techniques may be suitable for use in research, but it is virtually impossible to implement them in any larger scale for production of CaP coatings. The methods are generally expensive due to the cost of the ion guns and they are also rather slow. A typical deposition velocity is approximately 4 nm/min for an ion beam assisted sputter deposited coating, see for instance JP-PS 2562283 (Ektessabi). The deposition velocity of ion beam sputtered coatings is typically an order of magnitude lower (approximately 0.4 nm/min).
Wet Chemical Coating Methods
The wet chemical coating methods, such as dipping of samples into a sol solution, precipitation from supersturated solutions and electrolytically assisted CaT deposition techniques, are powerful methods which are well suited for use in a large scale coating fabrication, and in principle it is possible to coat also substrates with a complex shape by means of these techniques. However, up to date, each of these wet methods suffers from specific drawbacks which have to be eliminated before they can be used routinely for calcium-phosphate coating.
Drawbacks with the wet chemical methods are the poor adhesion between the substrate and the coating, the low deposition velocity, difficulties to obtain films covering the entire substrate, that the apatite films consist of small sharp-edged crystallites, 2 xcexcm-15 xcexcm large and that the films do not appear coherent, but the grains seem to consist of piled crystallites.
Finally, it is extremely difficult to produce a coating which is free from contaminants stemming from the impurity ions dissolved in the solutions used, e.g. Mg, Si etc. It is virtually impossible not to modify the original surface stochiometry of the substrate by the simultaneous CaP adsorption of other ions from the solution. Thus in case of coating dissolution in vivo the substrate surface exposed will not be the one which is originally used or prepared, with regard to oxide composition and surface chemistry. It should be understood that such modification of the underlying surface is not acceptable according to our objectives as it might jeopardize the long term stability conditions for the implant device in question.
RF-sputtering
RF-sputtering techniques are previously described in, e.g.,
1. J. G. C. Wolke, K. van Dijk, H. G. Schaeken, K. de Groot and J. A. Jansen, xe2x80x9cStudy of the surface characteristics of magnetron-sputter calcium phosphate coatingsxe2x80x9d, J. of Biomedical Materials Research, 28(1994) p. 1477,
2. K. van Dijk, H. G. Schaeken, J. G. C. Wolke, K. de Groot and J. A. Jansen, xe2x80x9cInfluence of discharge power level on the properties of hydroxyapatite-films deposited on Ti6A14V with RF magnetron sputteringxe2x80x9d, J. of Biomedical Materials Research, 29(1995) p. 269, and
3. K. van Dijk, H. G. Schaeken, J. G. C. Wolke and J. A. Jansen, xe2x80x9cInfluence of annealing temperature on RF magnetron sputtered calcium phosphate coatingsxe2x80x9d, Biomaterials, 17(1996) p. 405.
These three references solely rely on physical vapour deposition. Nobel gas (Ar) is used for the RF-sputtering. When pure Ar-gas is used during the RF-sputtering process Ca/P values of approximately 2.05 (xc2x10.15) are reported. This high Ca/P ratio is due to the fact that there occur preferential losses of e.g. POx and OH groups during the sputtering procedure (as well as during the plasma spraying and laser ablation techniques discussed above). Such losses result in high Ca/P ratios and negligible intensities of OH-vibrations in the FTIR spectra. Thus, using pure Ar-gas during the RF-sputtering process would give Ca/P values substantially higher than pure HA and the Ca/P ratio found in human bone, i.e. Ca/P=1.67. It should also be mentioned that the deposition velocities reported in the two first-mentioned references are 200 nm/min-250 nm/min.
The after-treatment of the coatings reported in ref.1 consists of an annealing xe2x80x9cin airxe2x80x9d. In ref.3 a heating cell is used which is kept in a humid atmosphere. A decrease of Ca/P stochiometry upon heating from approximately 2.1 to 1.94 is reported at temperatures around 600xc2x0 C.
In J. E. G. Hulshoff xe2x80x9cOsteocapacity of calcium phosphate coatingsxe2x80x9d, Thesis Catholic University Nijmegen, 1997, it is presented a coating preparation technique using RF magnetron sputtering where small amounts of water vapour or small amounts of oxygen were added to the argon (main gas carrier). However, the Ca/P ratios obtained by this coating preparation technique, see chapter 7 in Hulshoff et al, were also substantially higher than the Ca/P ratio found in human bone.
Furthermore, we note that the FTIR spectra from the coating produced by Hulshoff et al differs significantly from previously published FTIR spectra of typical calcium phosphates, as described by e.g. P. Ducheyne, W. van Raemdonck, J. C. Heughebaert and M. Heughebaert, xe2x80x9cStructural analysis of hydroxyapatite coatingsxe2x80x9d, Biomaterials, 7(1986) p.97, (see FIG. 7 in their article). The phosphate and hydroxyl bands, characteristic of typical calcium-phosphates and HA, seem to be absent in the FTIR spectra obtained from the coatings produced by Hulshoff et al. Specific combinations of CaP coatings with underlying substrate surfaces which would provide an optimal biological response was not presented by Hulshoff et al.
An object of the present invention is to provide a thin calcium phosphate coating on a clinically well documented implant element surface and which thereby combines properties for rapid bone growth during the early healing phase with the long term stability during clinical loading conditions for the well documented implant surface. Another object of the invention is to provide a comparatively thin coating which adheres well to the underlying implant surface, covers the surface as completely as possible and follows the implant surface morphology. A further object of the present invention is to provide a thin coating with a Ca/P ratio which is variable in a controlled manner. A desired crystallization of the coating would be achieved by a suitable after-treatment.
According to the invention a sputtering technique is used for providing a calcium-phosphate coating having a thickness from a few xc3x85ngstrxc3x6m and more. Specifically, a RF-sputtering technique is used and the coating is chemically modified by mixing the Ar-gas with oxygen and hydrogen gases resulting in a preferred Ca/P ratio. An annealing after-treatment of the coated implant devices is performed in a specially designed flow cell at a high temperature.